Cheng Sulin, Wiklund Petri, Autio Reija, Borra Ronald, Ojanen Xiaowei, Xu Leiting, Törmäkangas Timo, Alen Markku
Exercise Health and Technology Centre, Shanghai Jiao Tong University, Shanghai, China; Department of Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland.
Department of Health Sciences, University of Jyvaskyla, Jyvaskyla, Finland.
PLoS One. 2015 Oct 6;10(10):e0138889. doi: 10.1371/journal.pone.0138889. eCollection 2015.
Fatty liver is a major cause of obesity-related morbidity and mortality. The aim of this study was to identify early metabolic alterations associated with liver fat accumulation in 50- to 55-year-old men (n = 49) and women (n = 52) with and without NAFLD.
Hepatic fat content was measured using proton magnetic resonance spectroscopy (1H MRS). Serum samples were analyzed using a nuclear magnetic resonance (NMR) metabolomics platform. Global gene expression profiles of adipose tissues and skeletal muscle were analyzed using Affymetrix microarrays and quantitative PCR. Muscle protein expression was analyzed by Western blot.
Increased branched-chain amino acid (BCAA), aromatic amino acid (AAA) and orosomucoid were associated with liver fat accumulation already in its early stage, independent of sex, obesity or insulin resistance (p<0.05 for all). Significant down-regulation of BCAA catabolism and fatty acid and energy metabolism was observed in the adipose tissue of the NAFLD group (p<0.001for all), whereas no aberrant gene expression in the skeletal muscle was found. Reduced BCAA catabolic activity was inversely associated with serum BCAA and liver fat content (p<0.05 for all).
Liver fat accumulation, already in its early stage, is associated with increased serum branched-chain and aromatic amino acids. The observed associations of decreased BCAA catabolism activity, mitochondrial energy metabolism and serum BCAA concentration with liver fat content suggest that adipose tissue dysfunction may have a key role in the systemic nature of NAFLD pathogenesis.
脂肪肝是肥胖相关发病和死亡的主要原因。本研究的目的是确定50至55岁患有和未患有非酒精性脂肪性肝病（NAFLD）的男性（n = 49）和女性（n = 52）中与肝脏脂肪堆积相关的早期代谢改变。
使用质子磁共振波谱（1H MRS）测量肝脏脂肪含量。使用核磁共振（NMR）代谢组学平台分析血清样本。使用Affymetrix微阵列和定量PCR分析脂肪组织和骨骼肌的全局基因表达谱。通过蛋白质印迹分析肌肉蛋白表达。
支链氨基酸（BCAA）、芳香族氨基酸（AAA）和血清类粘蛋白增加与肝脏脂肪堆积的早期阶段相关，与性别、肥胖或胰岛素抵抗无关（所有p<0.05）。在NAFLD组的脂肪组织中观察到BCAA分解代谢以及脂肪酸和能量代谢的显著下调（所有p<0.001），而在骨骼肌中未发现异常基因表达。BCAA分解代谢活性降低与血清BCAA和肝脏脂肪含量呈负相关（所有p<0.05）。
肝脏脂肪堆积在其早期阶段就与血清支链和芳香族氨基酸增加有关。观察到的BCAA分解代谢活性降低、线粒体能量代谢和血清BCAA浓度与肝脏脂肪含量之间的关联表明，脂肪组织功能障碍可能在NAFLD发病机制的全身性中起关键作用。
